The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with pesticides and other agricultural exposures. The study is funded by the National Cancer Institute and the National Institute of Environmental Health Sciences, with collaboration from the US Environmental Protection Agency and the National Institute for Occupational Safety and Health. We are examining cancer incidence and other health endpoints in licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Between 1993 and 1997, we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and two-third also provided data on reproductive health, including information on all children under age 21 at time of enrollment. After enrollment, study participants completed up to three follow-up surveys in 1999-2003, 2005-2010, and 2013-2015 respectively. At each follow-up survey, study participants updated farming exposures and lifestyle and reported the occurrence of cancer, Parkinsons disease, and other chronic conditions. In addition to active follow-ups, the cohort is linked to population-based cancer registries in IA and NC and vital statistics to identify cancer cases and deaths. We also collected buccal-cell samples for genetic research from about 40% of the study participants and conducted a dietary survey as part of the 1999-2003 follow-up. Additionally, we have been collecting DNA samples on a regular basis from participants who developed specific cancers and other conditions. Finally, we conducted in-depth pesticide exposure assessment for selected chemicals in targeted samples of the cohort. Results of these assessments have been used to validate study questionnaires and inform exposure classification. In addition to cancer, the AHS has been investigating farming exposures in relation to neurological diseases and symptoms (Parkinson's disease, Alzheimer's disease, depression, neurobehavioral function, and suicide, amyotrophic lateral sclerosis), respiratory and allergic outcomes (asthma, rhinitis, and chronic bronchitis), cardiovascular disease (heart attack, stroke), diabetes (gestational and adult onset), autoimmune diseases (rheumatoid arthritis, lupus, and Sjogren's syndrome), age-related macular degeneration, fatal injury, and adverse reproductive outcomes (infertility, fibroids and endometriosis. This work is led by NIEHS investigators. NIEHS investigators have also been conducting sub-studies within AHS. In the Growth and Puberty (GAP) Study, a pilot study to assess the feasibility of measuring early puberty markers (hormone levels in urine and saliva, height velocity, Tanner staging), we enrolled and followed 60 children. Hormone assays were recently completed and their use in predicting puberty onset is being explored; preliminary findings were presented at a scientific meeting and a manuscript is in preparation. Data analysis continues for the Farming and Movement Evaluation (FAME) study while new cases of Parkinson's disease continue to be captured (see report by F Kamel)and validated in the AHS. Data collection for an in-depth study of respiratory diseases (The Lung Health Study) was recently completed (see report by S London, with findings related to genomics and endotoxin exposures submitted for publication. In 2015, the AHS started a new sub-study to investigate potential associations of pesticide exposures with dementia and Alzheimer's disease. We have screened the cognitive function of nearly 2500 elderly participants and identified about 16% with possible Alzheimers disease. This collaboration is led by Dr. Plassman at Duke University and Dr. Kamel at NIEHS. The AHS cohort continues to participate in large data pooling projects through the NCI-sponsored Cohort Consortium. In addition, the Agricultural Health Study is one of the founding members of the Agricultural cohort consortium (AGRICOH) and we hope to use this collaboration to enhance our ability to assess rare exposures and outcomes. To date, the Agricultural Health Study has published more than 200 scientific papers and NIEHS investigators contributed to 15 papers in the past year. These publications cover a range of health conditions such as cancer, end-stage renal disease, and rheumatoid arthritis. For example, we reported that in female spouses rheumatoid arthritis (RA) risk was associated with ever use of the fungicide maneb/mancozeb and the herbicide glyphosate, and use of chemical fertilizers and solvents, while women with lifetime exposure to life stock had a lower risk of RA (Parks et al, Environmental Health perspectives). We also reported associations between specific pesticides and end stage renal disease in spouses, findings that are consistent with previous observations among the farmer-applicators themselves. In addition, the AHS continuously reported findings on cancer outcomes either independently or as part of large international consortium. Over the years, the Agricultural Health Study has contributed to our knowledge on potential health effects of exposures that are associated with pesticides use and other farming activities. This continuously serves our ultimate goal to improve the health of US farmers and their family members. In the coming months, research will focus on confirming self-reported cases of specific autoimmune diseases and neurological disease to continue to explore the impact of agricultural exposures on health.